It is a privilege to be able to contribute to this volume in which Professor Zervas’ friends, students, and colleagues have joined together to honor him and his remarkable contributions to peptide chemistry. Although I did not know him until after his days in the Bergmann Laboratory at the Rockefeller Institute, I can claim the distinction of now working in those very same rooms that they occupied back in the mid-1930s. Like all peptide chemists, I am greatly indebted to Professor Zervas, having depended so heavily on the carbobenzoxy group and on the various modified urethan protecting groups which have been direct extensions of the revolutionary advance that Bergmann and Zervas made.

Solid-phase peptide synthesis.

As part of the dramatic changes associated with the need for preparing compound libraries in pharmaceutical and agrochemical research laboratories, industry searches for new technologies that allow for the automation of synthetic processes. Since the pioneering work by Merrifield polymeric supports have been identified to play a key role in this field however, polymer-assisted solution-phase synthesis which utilizes immobilized reagents and catalysts has only recently begun to flourish. Polymer-assisted solution-phase synthesis has various advantages over conventional solution-phase chemistry, such as the ease of separation of the supported species from a reaction mixture by filtration and washing, the opportunity to use an excess of the reagent to force the reaction to completion without causing workup problems, and the adaptability to continuous-flow processes. Various strategies for employing functionalized polymers stoichiometrically have been developed. Apart from reagents that are covalently or ionically attached to the polymeric backbone and which are released into solution in the presence of a suitable substrate, scavenger reagents play an increasingly important role in purifying reaction mixtures. Employing functionalized polymers in solution-phase synthesis has been shown to be extremely useful in automated parallel synthesis and multistep sequences. So far, compound libraries containing as many as 88 members have been generated by using several polymer-bound reagents one after another. Furthermore, it has been demonstrated that complex natural products like the alkaloids (+/-)-oxomaritidine and (+/-)-epimaritidine can be prepared by a sequence of five and six consecutive polymer-assisted steps, respectively, and the potent analgesic compound (+/-)-epibatidine in twelve linear steps ten of which are based on functionalized polymers. These developments reveal the great future prospects of polymer-assisted solution-phase synthesis.

Functionalized Polymers—Emerging Versatile Tools for Solution-Phase Chemistry and Automated Parallel Synthesis

The DNA/RNA Synthesizer provides a complete and automated procedure for the synthesis of DNA sequences. Each base unit is added in a 30-minute cycle, permitting a tetradecamer to be constructed in 6 1/2 hours. The complete procedure is described, including a practical procedure for isolation and purification of the desired DNA sequence.

https://science.sciencemag.org/content/sci/214/4518/270.full.pdf

Automated synthesis of gene fragments

Peptides are a very important biologically active class of naturally occurring compounds, and the number of newly discovered peptides has grown rapidly. The need for a large number of synthetic peptides and peptide analogs has grown even faster, and the most effective preparative methods are essential. This chapter describes solid-phase peptide synthesis. In the original and simplest form, solid-phase peptide synthesis involves a heterogeneous reaction mixture composed of an insoluble resin-bound peptide chain, a soluble activated amino acid derivative, and a solvent. The solid-phase principle for peptide synthesis was conceived and developed for providing a rapid, simplified, and effective way to prepare peptides and small proteins. This chapter focuses on solid supports, methods for attachment and removal of the peptide chain, protecting group schemes, and coupling methods. It also discusses difficult couplings and peptide ligation methods. The chapter also describes special synthetic applications including protein–nucleic acid compounds and the de novo design and synthesis of peptides and proteins.

W. Parr

Papers

A new solid support for polypeptide synthesis

Synthetic peptide amides by direct ammonolysis from the polystyrene-divinylbenzene resin